FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration

被引：197

作者：

Urwin, Hazel ^{[1
]}

Josephs, Keith A. ^{[5
]}

Rohrer, Jonathan D. ^{[2
]}

Mackenzie, Ian R. ^{[7
]}

Neumann, Manuela ^{[8
]}

Authier, Astrid ^{[1
]}

Seelaar, Harro ^{[9
]}

Van Swieten, John C. ^{[9
]}

Brown, Jeremy M. ^{[10
]}

Johannsen, Peter ^{[11
]}

Nielsen, Jorgen E. ^{[11
,12
]}

Holm, Ida E. ^{[13
]}

Dickson, Dennis W. ^{[14
]}

Rademakers, Rosa ^{[14
]}

Graff-Radford, Neill R. ^{[14
]}

Parisi, Joseph E. ^{[6
]}

Petersen, Ronald C. ^{[5
]}

Hatanpaa, Kimmo J. ^{[15
]}

White, Charles L., III ^{[15
]}

Weiner, Myron F. ^{[16
,17
]}

Geser, Felix ^{[18
]}

Van Deerlin, Vivianna M. ^{[18
]}

Trojanowski, John Q. ^{[18
]}

Miller, Bruce L. ^{[19
]}

Seeley, William W. ^{[19
]}

van der Zee, Julie ^{[20
,21
]}

Kumar-Singh, Samir ^{[20
,21
]}

Engelborghs, Sebastiaan ^{[21
,22
]}

De Deyn, Peter P. ^{[21
,22
]}

Van Broeckhoven, Christine ^{[20
,21
]}

Bigio, Eileen H. ^{[23
]}

Deng, Han-Xiang ^{[24
]}

Halliday, Glenda M. ^{[25
]}

Kril, Jillian J. ^{[26
]}

Munoz, David G. ^{[27
]}

Mann, David M. ^{[28
]}

Pickering-Brown, Stuart M. ^{[29
]}

Doodeman, Valerie ^{[30
]}

Adamson, Gary ^{[1
]}

Ghazi-Noori, Shabnam ^{[1
]}

Fisher, Elizabeth M. C. ^{[3
]}

Holton, Janice L. ^{[4
]}

Revesz, Tamas ^{[4
]}

Rossor, Martin N. ^{[2
]}

Collinge, John ^{[1
,3
]}

Mead, Simon ^{[1
]}

Isaacs, Adrian M. ^{[1
]}

机构：

[1] UCL Inst Neurol, MRC Prion Unit, London WC1N 3BG, England

[2] UCL Inst Neurol, Dementia Res Ctr, London WC1N 3BG, England

[3] UCL Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England

[4] UCL Inst Neurol, Dept Neuropathol, London WC1N 3BG, England

[5] Mayo Clin, Dept Neurol, Rochester, MN USA

[6] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA

[7] Univ British Columbia, Dept Pathol & Lab Med, Vancouver Gen Hosp, Vancouver, BC V5Z 1M9, Canada

[8] Univ Zurich Hosp, Inst Neuropathol, CH-8091 Zurich, Switzerland

[9] Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands

[10] Addenbrookes Hosp, Dept Neurol, Cambridge, England

[11] Copenhagen Univ Hosp, Memory Disorders Res Unit, Dept Neurol, Copenhagen, Denmark

[12] Univ Copenhagen, Dept Cellular & Mol Med, Neurogenet Sect, Panum Inst, Copenhagen, Denmark

[13] Aarhus Univ Hosp, Dept Pathol, Randers Hosp, Randers & Lab Expt Neuropathol,Danish Neurosci Ct, DK-8000 Aarhus, Denmark

[14] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA

[15] Univ Texas SW Med Sch, Dept Pathol, Dallas, TX USA

[16] Univ Texas SW Med Sch, Dept Psychiat, Dallas, TX USA

[17] Univ Texas SW Med Sch, Dept Neurol, Dallas, TX USA

[18] Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[19] UCSF, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA

[20] VIB, Dept Mol Genet, Neurodegenerat Brain Dis Grp, Antwerp, Belgium

[21] Univ Antwerp, Inst Born Bunge, B-2020 Antwerp, Belgium

[22] ZNA Middelheim, Dept Neurol, Memory Clin, Antwerp, Belgium

[23] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA

[24] Northwestern Univ, Dept Neurol & Clin Neurosci, Feinberg Sch Med, Chicago, IL 60611 USA

[25] Univ New S Wales, Prince Wales Med Res Inst, Sydney, NSW, Australia

[26] Univ Sydney, Disciplines Med & Pathol, Sydney, NSW 2006, Australia

[27] Univ Toronto, St Michaels Hosp, Dept Pathol, Toronto, ON M5B 1W8, Canada

[28] Univ Manchester, Clin Neurosci Res Grp, Sch Translat Med, Greater Manchester Neurosci Ctr, Salford, Lancs, England

[29] Univ Manchester, Clin Neurosci Res Grp, Fac Human & Med Sci, Manchester M13 9PT, Lancs, England

[30] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands

来源：

ACTA NEUROPATHOLOGICA | 2010年 / 120卷 / 01期

基金：

美国国家卫生研究院; 英国医学研究理事会;

关键词：

FTLD; FUS; FTLD-UPS; Frontotemporal; FTD; MOTOR-NEURON DISEASE; FILAMENT INCLUSION DISEASE; PICKS-DISEASE; GENE-MUTATIONS; BODY DISEASE; FTLD-U; DEMENTIA; PROGRANULIN; TDP-43; HETEROGENEITY;

D O I：

10.1007/s00401-010-0698-6

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Through an international consortium, we have collected 37 tau- and TAR DNA-binding protein 43 (TDP-43)-negative frontotemporal lobar degeneration (FTLD) cases, and present here the first comprehensive analysis of these cases in terms of neuropathology, genetics, demographics and clinical data. 92% (34/37) had fused in sarcoma (FUS) protein pathology, indicating that FTLD-FUS is an important FTLD subtype. This FTLD-FUS collection specifically focussed on aFTLD-U cases, one of three recently defined subtypes of FTLD-FUS. The aFTLD-U subtype of FTLD-FUS is characterised clinically by behavioural variant frontotemporal dementia (bvFTD) and has a particularly young age of onset with a mean of 41 years. Further, this subtype had a high prevalence of psychotic symptoms (36% of cases) and low prevalence of motor symptoms (3% of cases). We did not find FUS mutations in any aFTLD-U case. To date, the only subtype of cases reported to have ubiquitin-positive but tau-, TDP-43- and FUS-negative pathology, termed FTLD-UPS, is the result of charged multivesicular body protein 2B gene (CHMP2B) mutation. We identified three FTLD-UPS cases, which are negative for CHMP2B mutation, suggesting that the full complement of FTLD pathologies is yet to be elucidated.

引用

页码：33 / 41

页数：9

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